Patients with ST-segment elevation of myocardial infarction miss out on early reperfusion： when to undergo delayed revascularization

Objective There are still a high proportion of patients with ST-segment elevation myocardial infarction （STEMI） missing out early reperfusion even in the primary percutaneous coronary intervention （PCI） era. Most of them are stable latecomers, but the optimal time to undergo delayed PCI for stable ones remains controversial. Methods We investigated all STEMI patients who underwent delayed PCI （2-28 days after STEMI） during 2007-2010 in Beijing and excluded patients with hemodynamic instability. The primary outcome was maj or adverse cardiovascular events （MACEs）. Results This study finally enrolled 5,417 STEMI patients and assigned them into three groups according to individual delayed time （Early group, 55.9%; Medium group, 35.4%; Late group, 8.7%）. During 1-year follow-up, MACEs occurred in 319 patients. The incidence of MACEs were respectively 7.1%, 5.6% and 6.7% among three groups. The Medium group had less recurrent myocardial infarction plus cardiac death （hazard ratio, 0.525; 95% confidence interval, 0.294-0.938, P = 0.030） than Late group and less repeat revascularization （hazard ratio, 0.640; 95% confidence interval, 0.463-0.883, P = 0.007） than Early group in pairwise comparisons. We depicted the incidence of major adverse cardiovascular event （MACE） by delayed time as a quadratic curve and found the bottom appeared at day 14. Conclusions The delayed PCI time varied in the real-world practice, but undergoing operations on the second week after STEMI had greater survival benefit and less adverse events for whom without early reperfusion and hemodynamic instability.

Animal exercise studies in cardiovascular research:Current knowledge and optimal design--A position paper of the Committee on Cardiac Rehabilitation,Chinese Medical Doctors’Association

Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However,the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated.Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection.However,standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective,high-quality animal studies using exercise to prevent and treat cardiovascular diseases.In our review,we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training,emphasizing the appropriate measurements and analysis in these chronic exercise models.We also provide recommendations for optimal design of animal exercise studies in cardiovascular research,including the choice of exercise models,control of exercise protocols,exercise at different stages of disease,and other considerations,such as age,sex,and genetic background.We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases.

Opportunity and challenge of rehabilitation medicine in China

Rehabilitation medicine is an emerging discipline in China which is just like most countries in the world.With China’s reform and opening up,economic development,and the increasing demand for health among the people,rehabilitation medicine which focuses on functional recovery has gradually attracted the attention of society and the people.

Comparison of intraosseous access and central venous catheterization in Chinese adult emergency patients: A prospective, multicenter, and randomized study

BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous(IO) access and central venous catheterization(CVC) in critically ill Chinese patients.METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above.RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group(91.7% vs. 50.0%, P<0.001;52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion(1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups.CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.

A case of applying left bundle branch pacing combined with atrioventricular node ablation to treat atrial fibrillation-induced heart failure

The core treatment of rapid arrhythmiainduced heart failure(HF)is to control the ventricular rate to an optimized lower level,which is usually achieved with various anti-arrhythmic drugs.However,arrhythmias may not respond well to pharmaceutical treatment for various reasons.Iatrogenic atrioventricular(AV)node ablation needs to be performed under these extreme conditions to lower the patient’s heart rate.

Expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics

Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.

Multidisciplinary team management and long-term prognosis of an elderly patient with severe cardiac amyloidosis complicated with multiple myeloma

Immunoglobulin light chain amyloidosis(AL)is one of the most frequent causes of cardiac amyloidosis(CA),[1]with an estimated prevalence of 8 to 12 per million.[2−4]Multiple myeloma(MM)is hematological neoplasia originating from plasma cells,which is the most common disease that can lead to CA.The median age of patients with MM at diagnosis is about 65 years old.In this age group,cardiovascular diseases often co-exist,increasing the risk of adverse events related to MM treatment.By convention,the prognosis of AL-CA with MM is extremely poor,with a median survival time of five months.[5]The degree of cardiac involvement has a decisive impact on the prognosis of AL-CA pati-ents.

Assessment of causal direction between thyroid function and cardiometabolic health:a Mendelian randomization study

BACKGROUND Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remains partly unknown.METHODS The Mendelian randomization(MR)was used to test genetic,potentially causal relationships between instrumental variables and cardiometabolic traits.Genetic variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental variables.Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen,CARDIoGRAM and CARDIoGRAMplusC4D,CHARGE,and MEGASTROKE.This study was conducted using summary statistic data from large,previously described cohorts.Association between thyroid function and essential hypertension(EHTN),secondary hypertension(SHTN),hyperlipidemia(HPL),type 2 diabetes mellitus(T2DM),ischemic heart disease(IHD),myocardial infarction(MI),heart failure(HF),pulmonary heart disease(PHD),stroke,and non-rheumatic valve disease(NRVD)were examined.RESULTS Genetically predicted FT4 levels were associated with SHTN(odds ratio=0.48;95%CI=0.04−0.82,P=0.027),HPL(odds ratio=0.67;95%CI=0.18−0.88,P=0.023),T2DM(odds ratio=0.80;95%CI=0.42−0.86,P=0.005),IHD(odds ratio=0.85;95%CI=0.49−0.98,P=0.039),NRVD(odds ratio=0.75;95%CI=0.27−0.97,P=0.039).Additionally,genetically predicted TSH levels were associated with HF(odds ratio=0.82;95%CI=0.68−0.99,P=0.042),PHD(odds ratio=0.75;95%CI=0.32−0.82,P=0.006),stroke(odds ratio=0.95;95%CI=0.81−0.97,P=0.007).However,genetically predicted thyroid function traits were not associated with EHTN and MI.CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

Analysis of risk factors for early stent thrombosis in the Chinese population:A multicenter restrospective study

BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention(PCI).Patients from ten Chinese hospitals diagnosed as stent thrombosis(ST)from January 2010 to December 2016 were retrospectively included as the study group.A control group(1 case:2 controls)was created by including patients without ST,major adverse cardiovascular events,or cerebrovascular events during follow-up.The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients,who were included to identify factors that predicted EST and to develop a prediction scoring system.The other 171 patients without integrated 1:2 pair were used for external validation.RESULTS:EST was independently associated with a low hemoglobin concentration(adjusted odds ratio[OR]0.946,95%confi dence interval[95%CI]0.901-0.993,P=0.026),a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score(OR 1.166,95%CI 1.049-1.297,P=0.004),and a DAPT(DAPT)duration of<30 days(OR 28.033,95%CI 5.302-272.834,P<0.001).The simple EST prediction score provided an area under the curve(AUC)of 0.854(95%CI 0.777-0.932,P<0.001)with 70.0%sensitivity and 90.0%specifi city,and 0.742(95%CI 0.649-0.835,P<0.001)with 54.5%sensitivity and 81.0%specifi city for external validation dataset.CONCLUSIONS:EST may be independently associated with DAPT discontinuation within 30 days,a low hemoglobin concentration,and a high SYNTAX score.The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.

ROS does not contribute to acute development of nitroglycerine tolerance in rat aortas

The development of nitroglycerine tolerance limits its clinical efficacy of nitric oxide(NO)donors. Several cellular mechanisms have been proposed to explain this phenomenon,one of which is an exaggerated production of reactive oxygen specious(ROS).The present study examined whether ROS contribute to the occurrence of nitroglycerine tolerance which is induced

Differential Proteomic Analysis of Neonatal Cardiomyocytes in Response to β-Adrenergic Receptor Stimulation

β-Adrenoceptors（β-ARs） play a critical role in regulating cardiac functions under both physiological and pathological conditions. To further explore the mechanisms through which β-ARs perform its actions, proteomic approaches were adopted to study the global protein patterns in cultured neonatal rat cardiomyocytes exposed to iseproterenol （ISO）. A modified method, ＂Mirror Images in One Gel＂, was used to improve the reproducibility and resolution power of two-dimensional electrophoresis. A 2-DE map with a good reproducibility was obtained in which 1281 ± 70 spots were detected and about 1191± 54 spots were matched, with an average matching rate of 92. 9%. Nine proteins with significant changes were identified by using peptide mass fingerprinting（PMF） data obtained vht MALDI-MS.

Hige namine as a Potential Pharmacologic Stress Age nt in the Detection of Coro nary Artery Disease

Myocardial perfusion imaging(MPI) is valuable for the diagnosis,prognosis,and management of coronary artery disease(CAD).The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic agents.However,these agents have contraindications and may cause adverse effects in some patients.Thus,other stress agents feasible for more patients are required.Higenamine(HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial infarction.It also has a promising value in MPI for the detection of CAD in preclinical and clinical studies.This review summarizes the application of HG on MPI,including its mechanism of action,stress protocol,efficacy,and safety.

Development and validation of a nomogram predicting oneyear mortality in patients undergoing percutaneous coronary intervention

OBJECTIVE To formulate a nomogram to predict the risk of one-year mortality after percutaneous coronary intervention(PCI)based on a large-scale real-world Asian cohort.METHODS This study cohort included consecutive patients undergoing PCI in the National Center for Cardiovascular Diseases of China.The endpoint was all-cause mortality.Least absolute shrinkage and selection operator Cox regression and backward stepwise regression were used to select potential risk factors.A nomogram based on the predictors was accordingly constructed to predict one-year mortality.The performance of the nomogram was evaluated.Patients were stratified into low-,intermediate-and high-risk groups according to the tertile points in the nomogram and compared by the Kaplan-Meier analysis.RESULTS A total of 9603 individuals were included in this study and randomly divided into the derivation cohort(60%)and the validation cohort(40%).Six variables were selected to formulate the nomogram,including age,renal insufficiency,cardiac dysfunction,previous cerebrovascular disease,previous PCI,and TIMI 0–1 before PCI.The area under the curve of this nomogram regarding one-year mortality risks were 0.792 and 0.754 in the derivation cohort and validation cohort,respectively.Kaplan-Meier curve successfully stratified the patients according to three risk groups.This nomogram calibrated well and exhibited satisfactory clinical utility in the decision curve analysis.CONCLUSIONS This study developed and validated a simple-to-use nomogram predicting one-year mortality risk in Asian patients undergoing PCI and could help clinicians make risk-dependent decisions.

Exercise training attenuates angiotensinⅡ-induced cardiac fibrosis by reducing POU2F1 expression

Background:Exercise training protects against heart failure.However,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains unclear.Methods:An exercise model involving C57BL/6N mice and 6 weeks of treadmill training was used.AngⅡ(1.44 mg/kg/day)was administered to induce cardiac fibrosis.RNA sequencing and bioinformatic analysis were used to identify the key factors mediating the effects of exercise training on cardiac fibrosis.Primary adult mouse cardiac fibroblasts(CFs)were used in vitro.Adeno-associated virus serotype 9 was used to overexpress POU domain,class 2,transcription factor 1(POU2F1)in vivo.Results:Exercise training attenuated AngⅡ-induced cardiac fibrosis and reversed 39 gene expression changes.The transcription factor regulating the largest number of these genes was POU2F1.Compared to controls,POU2F1 was shown to be signififcantly upregulated by AngⅡ,which is itself reduced by exercise training.In vivo,POU2F1 overexpression nullified the benefits of exercise training on cardiac fibrosis.In CFs,POU2F1 promoted cardiac fibrosis.CCAAT enhancer-binding proteinβ(C/EBPβ)was predicted to be the transcription factor of POU2F1and verified using a dual-luciferase reporter assay.In vivo,exercise training activated AMP-activated protein kinase(AMPK)and alleviated the increase in C/EBPβinduced by AngⅡ.In CFs,AMPK agonist inhibited the increase in C/EBPβand POU2F1 induced by Ang II,whereas AMPK inhibitor reversed this effect.Conclusion:Exercise training attenuates AngⅡ-induced cardiac fibrosis by reducing POU2F1.Exercise training inhibits POU2F1 by activating AMPK,which is followed by the downregulation of C/EBPβ,the transcription factor of POU2F1.

LLMs in medicine:The need for advanced evaluation systems for disruptive technologies

In an era of rapid advancements in artificial intelligence(AI),the potential role of large language models(LLMs)in the medical field is receiving increasing attention.The progression of this technology not only highlights upcoming revolutionary changes in medical services but also offers unprecedented opportunities for the health care sector.1 LLMs’formidable capability to process natural language opens vast prospects for application in the medical field,including in the contexts of emergency triage,geriatric care,and digital medical workflows.

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients

Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.

Increased telocytes involved in the proliferation of vascular smooth muscle cells in rat carotid artery balloon injury

Telocytes （TCs） are a novel type of interstitial cells that are thought to be involved in tissue regeneration and repair. However, the possible roles of TCs in vascular diseases remain unclear. In this study, we used a rat model of carotid artery balloon injury （CABI） to study the changes and potential roles of vascular TCs after vascular injury. Transmission electron microscopy （TEM） and CD34/vimentin immunolabeling were used to identify and quantify TCs in normal and injured carotid arteries. Quantita- tive immunofluorescence analysis revealed that, compared with the sham group, the number of TCs in the CAB1 group in- creased from 7.2＋1.0 to an average of 20.4＋1.8 per l-ram2 vascular area. The expression level of miR-24 in TCs was three times higher than in vascular smooth muscle cells （VSMCs）. The percentage of VSMCs in S phase and G2/M phase increased by approximately 5% when VSMCs were incubated with the supematant of TCs. The antagomir of miR-24 in TCs reduced the ratio of VSMCs in S ohase and G2/M phase. This study illuminates the function of TCs in the proliferation of VSMCs.

STUDY ON MECHANICAL INTERACTIONS BETWEEN SINGLE CARDIAC MYOCYTE AND ELASTIC SUBSTRATE

Quantitative investigation on mechanical characteristics of cardiac myocytes has important physiological significance. Based on elastic substrate technique, this paper develops a set of algorithms for high-efficiency cellular traction recovery. By applying a gradient-based digital image correlation method to track randomly distributed fluorescence microbeads on the deformed substrate induced by single cardiac myocyte, high-resolution substrate displacement field can readily be obtained. By using a numerical algorithm based on the integral Boussinesq solution, cell-substrate tractions are reconstructed in a stable and reliable manner. Finally, spatiotemporal dynamics of a single cardiac myocyte is investigated as it adheres to a polyacrylamide elastic substrate.

Higher serum angiopoietin 2 levels are independently associated with coronary microvascular dysfunction in patients with angina in the absence of obstructive coronary artery disease

Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study.Coronary flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography.The patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values<2.5 and the preserved CFR group with CFR values≥2.5.Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay.Independent predictors for impaired CFR were identified by binary logistic regression analysis.The receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P<0.001),and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR.Serum Ang-2 levels were negatively correlated with CFR(r=0.386,P<0.001).Binary logistic regression analysis showed that Ang-2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired CFR.Furthermore,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P<0.001).The area under the curve was 0.712(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.